Patients can also lie about their health to be accepted into a trial. Some even make their “living” going from one trial to another. The problem will continue, some observers say, until a national registry is put into place to catch these kinds of problems.

The focus on Phase I trials

Much of the issue surrounds Phase I clinical trials in which 20 to 80 healthy subjects test a drug for safety. These trials are not as well-regulated as later-phase trials. For example, Phase I trials are not required to be registered on the ClinicalTrials.gov website. They also are more often run by contract research organizations (CROs) rather than at medical centers. Plus they usually pay for participation.

One presentation at the 2013 meeting of the New Clinical Drug Evaluation Unit (NCDEU — now called the American Society of Clinical Psychopharmacology Annual Meeting) in Hollywood, Florida, looked at the characteristics of duplicate research subjects in the CTSdatabase registry.1 In this study, researchers entered subject-authorized partial identifiers of prescreening central nervous system (CNS) subjects, presenting at participating sites, into the CTSdatabase subject registry. All subjects and the subset of potential duplicate subjects were divided by gender and age into 10-year cohorts. The cohorts were then compared with each other and against data from the 2010 U.S. Census.

Researchers found that almost 69% of duplicate subjects were between the ages of 40 and 59. Although the most common duplicate subject was a male in his 40s, all ages and genders were shown to be among the duplicates. The researchers did wonder, however, if the economic downturn has resulted in more middle-aged men participating in the studies.1

Three-quarters of experienced subjects in one study said they have deceived researchers at some point so they would not be excluded from a clinical trial.2 For this study, the subjects must have enrolled in at least two clinical trials in the past year. Health problems were concealed by 32% of the subjects, use of prescribed medications by 28%, and recreational drug use by 20%. One quarter of subjects reported exaggerating symptoms so they could qualify for a study, and 14% reported pretending to have a health condition to qualify. The subjects did not give the frequency or context for their deception. The researchers thought it could be fueled in part by undue inducements, overly restrictive criteria for entry, and increased demand for healthy controls. “Understanding the context and frequency of deception will inform the extent to which it jeopardizes study integrity and safety,” the researchers say.

The professional guinea pig

While many research subjects enroll in a trial to help others or to possibly find a new treatment for their own disease of condition, some use trials as their primary source of income. In September 2015, The Atlantic magazine profiled the lives of several “professional guinea pigs” who go from trial to trial.3 These research participants report earning up to $20,000 a year, and they rely on other professional research subjects to find out where current trials are and what amenities they offer, such as computer access and video games. They coach each other on what to say to get into trials (don’t say you have ever smoked), how to prepare their bodies for screening (exercising can increase your creatinine levels), and what to say about your participation in other clinical trials (say you haven’t been in one since last year).

Professional research subject Robert Helms tells The Atlantic that he knows it sounds selfish, “but the way it works is, I’m working poor, and the people making the drugs are filthy rich, and I need a job.”3 He also defends subjects such as himself as “reliable.” “Pro guinea pigs, we come where we’re supposed to be on time, we’re not afraid of needles. When you explain something it’s going to be understood because you know what’s going on,” he says. “It’s not going to be a disaster. The way disasters happen is when a guy comes in and he doesn’t know the ropes.”

Carl Elliott, a professor in the Center for Bioethics and the Departments of Pediatrics and Philosophy at The University of Minnesota in Minneapolis, argues that “homeless people, undocumented people, people who are either temporarily or long-term unemployed, people who are out of jail who can’t get regular work” are the ones who have weeks to check-in and spend on a Phase I clinical trial. Elliott has even called for an overhaul of the way human subjects are treated, saying that studies on healthy patients are “best characterized as a kind of labor relation.”4

Roberto Abadie, research assistant professor at the Department of Sociology, University of Nebraska, Lincoln, believes that the pharmaceutical industry has become dependent on the experienced research subject. In research for his book, The Professional Guinea Pig, Abadie met research subjects who had participated in more than 80 Phase I clinical trials. Financial incentives compromise the ethical imperative for informed consent to be freely given by clinical trials subjects, Abadie says. However, he believes that ending the practice of paying research subjects would probably slow or stop the drug development process altogether.5

Like Elliott, Abadie advocates for better working conditions and proper compensation for the research subjects. He also suggests a central registry that documents the participation of paid volunteers in trials. “Of particular relevance is information about the identity of volunteers, as well as how often, where, and in which trials they participate. Data about ADRs (Adverse Drug Reactions) or other events should also be recorded.”5 Abadie does not address the issue of privacy concerns in such a registry.

Bioethicists David Resnik and Greg Koski also addressed the need for a national registry for healthy volunteers in Phase I clinical trials in a 2011 article in the Journal of the American Medical Association.6 “To adequately deal with the problem of overlapping enrollment, a national registry is needed,” they say. “The registry should be linked to databases that provide investigators with important information related to the studies in which an individual has participated, such as interventions, drugs, estimated duration of the research, and contact information. Costs would be modest and could be financed by fees from study sponsors.” Resnik and Koski recommend that federal agencies make participation in the national registry a requirement for conducting a Phase I trial enrolling healthy volunteers. “A national safety registry for study participants is a simple, straightforward way to minimize the risks and biases associated with overlapping enrollment in Phase I studies and can be implemented at a low cost with minimal additional burden on investigators or sponsors.”6

Resnik, a bioethicist at the National Institute of Environmental Health Sciences, further addressed the issue with David McCann, associate director of the National Institute on Drug Abuse. There are several strategies investigators can use to address the problem of deceptive behavior by research participants, they say.7 First, physical exams and lab tests can verify information given by research subjects. Second, researchers can exclude research subjects who lied from participating in the study. Third, researchers can offer rewards, such as gift cards, for subjects who were not found to be deceptive with their answers. Finally, Resnik and McCann say that investigators could require participants to be listed in a clinical trial participant registry that maintains records of study enrollment. “Such a database can be used to check for current enrollment in other studies and to ensure that an appropriate wash-out period has passed since a previous medication study.”

The registries offered by several companies are often underutilized and do not communicate with each other, they say. “Several countries and some U.S. academic institutions have implemented local registries of study participants, but the United States does not have a national registry. A national registry could play an important role in promoting research integrity and protecting subjects from harm.”7

References

1. Shiovitz TM, Manlosa NB, Gevorgyan L, et al. Characteristics of duplicate subjects in a clinical trial database. Presented at NCDEU, May 29, 2013. Available at: http://www.ctsdatabase.com/files/Characteristics%20of%20Duplicate%20Subjects%20in%20a%20Clinical%20Trial%20Subject%20Registry.pdf. Accessed Jan. 2, 2017.
2. Devine EG, Waters ME, Putnam M, et al. Concealment and fabrication by experienced research subjects. Clin Trials 2013;10:935-948.
3. Romm C. The Life of a Professional Guinea Pig. The Atlantic September 23, 2015. Available at http://www.theatlantic.com/science/archive/2015/09/life-of-a-professional-guinea-pig/406018/. Accessed Jan. 2, 2017.
4. Elliott C. Justice for the professional guinea pig. Am J Bioeth Published online December 7, 2010.
5. Abadie R. The “mid-torture economy”: Exploring the world of professional research subjects and its ethical implications Physis 2015;25;709-728.
6. Resnik DB, Koski G. A national registry for healthy volunteers in Phase 1 clinical trials. JAMA 2011;305:1236-37.
7. Resnik DB, Mccann DJ. Deception by research participants. N Engl J Med 2015;373:1192-93.

By Sue Coons, MA

This article was reprinted from Research Practitioner, Volume 18, Number 1, January-February 2017.